부산대학교 도서관

We have identified a new function for the dynein adaptor Bicaudal D homolog 1 ( BICD1) by screening a si RNA library for genes affecting the dynamics of neurotrophin receptor-containing endosomes in motor neurons ( MNs). Depleting BICD1 increased the intracellular accumulation of brain-derived neurotrophic factor ( BDNF)-activated Trk B and p75 neurotrophin receptor (p75 NTR) by disrupting the endosomal sorting, reducing lysosomal degradation and increasing the co-localisation of these neurotrophin receptors with retromer-associated sorting nexin 1. The resulting re-routing of active receptors increased their recycling to the plasma membrane and altered the repertoire of signalling-competent Trk B isoforms and p75 NTR available for ligand binding on the neuronal surface. This resulted in attenuated, but more sustained, AKT activation in response to BDNF stimulation. These data, together with our observation that Bicd1 expression is restricted to the developing nervous system when neurotrophin receptor expression peaks, indicate that BICD1 regulates neurotrophin signalling by modulating the endosomal sorting of internalised ligand-activated receptors. [ABSTRACT FROM AUTHOR]